Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct;41(2):469-478.
doi: 10.1007/s12028-024-01952-0. Epub 2024 Mar 5.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study

Matthew C Culkin  1   2 , Priyanka Bele  1   2 , Anastasia P Georges  2   3 , Patricia Santos  1   2 , Grace Niziolek  1 , Lewis J Kaplan  1 , Douglas H Smith  2 , Jose L Pascual  4   5
Affiliations

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study

Matthew C Culkin et al. Neurocrit Care. 2024 Oct.

Abstract

Background: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery.

Methods: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury.

Results: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group.

Conclusions: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

Keywords: Blood–brain barrier; Dosing; Leukocytes; Permeability; TBI; Tranexamic acid.

PubMed Disclaimer

References

    1. Gardner AJ, Zafonte R. Neuroepidemiology of traumatic brain injury. Handb Clin Neurol. 2016;138:207–23. https://doi.org/10.1016/B978-0-12-802973-2.00012-4 . - DOI - PubMed
    1. Injury GBDTB, Spinal Cord Injury C. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(1):56–87. https://doi.org/10.1016/S1474-4422(18)30415-0 . - DOI
    1. Sabet N, Soltani Z, Khaksari M. Multipotential and systemic effects of traumatic brain injury. J Neuroimmunol. 2021. https://doi.org/10.1016/j.jneuroim.2021.577619 . - DOI - PubMed
    1. McKee AC, Daneshvar DH. The neuropathology of traumatic brain injury. Amsterdam: Elsevier; 2015. p. 45–66.
    1. Shi K, Zhang J, Dong J-F, et al. Dissemination of brain inflammation in traumatic brain injury. Cell Mol Immunol. 2019;16(6):523–30. https://doi.org/10.1038/s41423-019-0213-5 . - DOI - PubMed - PMC

MeSH terms

LinkOut - more resources